Supplemental Table 1

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b) General characteristics of malignant NK cell lines. Cell line Gender. Age. Ethinicity Original diagnosis. CD56. CD3. EBV. IL2 dependency. NK92. M. 50.
Supplemental Table 1 a) Histopathological characteristics of NKTCL cases used in this study* Original TCR Pathology description Population Sex Biopsy site CD3e CD2 CD5 CD7 CD4 CD8 CD56 TiA1 EBV arrangement classification of disease by RNA-Seq

Case-1

NKTCL

France

M

Case-2

NKTCL

France

Case-3

NKTCL

Case-4

lymph node

-

+

-

-

-

-

NA

+

+

TCRαβ +

M nasal cavity

+

+

-

-

-

-

+

+

+

germline

France

M

+

-

-

NA

-

-

+

+

+

germline

NKTCL

France

M nasal cavity

-

+

-

-

-

-

+

+

+

germline

Case-5

NKTCL

France

M nasal cavity

+

+

-

+ NA NA

+

NA

+

germline

Case-6

NKTCL

France

F nasal cavity

+

+

-

-

+

+

+

germline

M

lymph node

+

+

-

-

-

-

+

+

TCRαβ +

+

+

-

+ NA

-

+

+

+

-

-

-

-

+

+

+

NA

-

-

+

-

-

+

NA

+

Case-7

NKTCL

France

skin

Case-8

NKTCL

France

M

lymph node

Case-9

NKTCL

France

M

lymph node

F Case-10

NKTCL

USA

Case-11

NKTCL

USA

small bowel

NA NA

-

NA NA*

germline

germline

germline

F nasal cavity

-

NA

-

NA

-

-

+

+

-

NA NA NA

+

+

+

germline

+

+

+

germline

Case-12

NKTCL

testis Hong Kong M (secondary)

Case-13

NKTCL

Hong Kong F

NA

NA

NA NA NA NA NA NA NA NA

germline

Case-14

NKTCL

Hong Kong M

NA

NA

NA NA NA NA NA NA NA NA

germline

Case-15

NKTCL

Hong Kong M

testis (secondary)

+

+

-

-

-

-

+

+

+

Case-16

NKTCL

Hong Kong F nasal cavity

+

+

-

+

-

-

+

+

+

germline

Case-17

NKTCL

Hong Kong M nasal cavity

+

+

-

-

-

+

+

+

germline

germline

* : This table was reported earlier by Küçük et al. Am. J. Pathol. 2016. NA: Not available.

b) General characteristics of malignant NK cell lines Cell line

Gender

Age

Ethinicity

NK92

M

50

Caucasian

KHYG1

F

45

Japanese

Original diagnosis Non nasal NKTCL

CD56

CD3

EBV

IL2 dependency

+

-

+

+

ANKL

+

-

-

+

Supplemental Table 2 a) List of lncRNAs significantly overexpressed (> 2 fold) in NKTCL cases compared to those in normal NK cells lncRNA name CTD-2540B15.11 RP11-291B21.2 CTD-2369P2.8 SNHG5 RP11-626G11.3 RP11-746M1.1 RP4-738P15.6 CTD-2017F17.2 CTD-2369P2.4 RP11-580I16.2 RP11-161H23.5 RP5-940J5.9 RAB30-AS1 RP11-192H23.5 RP11-25K21.6 AC010761.8 RP11-19P22.8 RP11-300J18.2 ARAP1-AS1 RP11-203M5.8 AC007620.3 RP5-1074L1.4 GAS5 AC005253.4 RP11-264I13.2 RP11-334E6.10 SNHG19 RP1-30M3.5 RP11-119K6.6 LINC00854 CTC-444N24.11 RP11-498C9.13 RP11-258C19.7 RP11-629O1.2 IL21R-AS1 PAX8-AS1 LRRC75A-AS1 RP11-6N17.4

Normal NK cell median expression level (FPKM) 1.33 8.02 1.43 41.56 2.00 3.69 4.13 1.96 2.14 1.71 4.07 265.01 2.04 2.36 1.57 4.59 3.81 1.28 9.93 1.84 4.22 1.84 88.34 4.81 1.15 2.13 9.88 2.42 1.31 1.24 2.26 2.46 1.33 1.26 1.48 1.26 72.51 1.20

NKTCL median expression level (FPKM) 13.31 79.61 10.15 229.74 10.81 18.26 20.04 9.47 9.96 7.96 18.88 1173.50 9.00 10.32 6.74 18.36 15.02 4.92 37.99 6.92 15.08 6.42 307.88 16.70 3.97 7.23 32.76 8.02 4.34 4.08 7.27 7.59 4.10 3.87 4.53 3.85 214.14 3.50

The ratio of median expression value (NKTCL/normal NK) 10.02 9.93 7.12 5.53 5.42 4.95 4.85 4.84 4.65 4.64 4.64 4.43 4.42 4.38 4.30 4.00 3.94 3.86 3.83 3.76 3.58 3.49 3.49 3.47 3.47 3.40 3.32 3.31 3.31 3.28 3.21 3.08 3.08 3.07 3.06 3.04 2.95 2.92

t-test 0.0003 0.0041 0.0008 0.0066 0.0206 0.0000 0.0000 0.0000 0.0000 0.0000 0.0163 0.0034 0.0000 0.0091 0.0473 0.0000 0.0000 0.0013 0.0000 0.0000 0.0098 0.0038 0.0000 0.0005 0.0004 0.0005 0.0051 0.0000 0.0096 0.0031 0.0000 0.0055 0.0053 0.0001 0.0194 0.0008 0.0004 0.0000

RP11-6N17.9 AC007246.3 RP11-282O18.3 CTA-384D8.36 CTD-2576D5.4 SNHG8 LINC00539 RP11-305L7.1 RP1-20B21.4 RP11-661A12.8 LIPE-AS1 RP5-1024G6.2 RP11-498C9.3 PRMT5-AS1 CTB-179K24.3 RP11-126K1.8 RP5-1028K7.2 LINC00467 RP11-644F5.11 RP11-627K11.6 ZBED5-AS1 RP11-802E16.3 ZFAS1 RP11-488C13.5 RP11-552M11.4 AC133528.2 RP11-368P15.3 CTB-12A17.3 CTC-444N24.8 AC005339.2 AC005104.3 CDC37L1-AS1 CTD-2006H14.2 AC000120.7 RP11-973H7.4 ZSCAN16-AS1 LINC00847 RP11-186B7.4 CTD-2514K5.4 CTA-363E6.7 RUSC1-AS1 RP11-620J15.3 RP11-109P14.9 TMEM44-AS1 LINC00174

5.91 1.38 4.29 2.00 1.17 31.24 2.09 1.61 12.30 3.17 2.42 2.76 8.02 1.30 1.53 5.66 6.16 1.53 2.60 7.62 1.96 4.36 39.99 4.75 9.24 2.07 2.19 10.13 1.04 3.20 1.18 1.55 1.20 1.30 1.35 1.93 5.37 67.15 1.57 6.85 5.41 10.31 2.48 1.32 1.25

16.92 3.96 12.09 5.61 3.25 86.38 5.71 4.36 33.19 8.49 6.42 7.30 20.76 3.34 3.90 14.42 15.60 3.86 6.52 19.02 4.88 10.76 98.34 11.65 22.49 4.96 5.25 23.88 2.41 7.31 2.67 3.52 2.72 2.85 2.95 4.17 11.52 143.83 3.36 14.57 11.46 21.79 5.20 2.77 2.60

2.87 2.86 2.81 2.80 2.79 2.77 2.74 2.71 2.70 2.68 2.65 2.64 2.59 2.58 2.55 2.55 2.53 2.52 2.51 2.50 2.49 2.47 2.46 2.45 2.44 2.40 2.39 2.36 2.32 2.28 2.26 2.26 2.26 2.19 2.18 2.16 2.15 2.14 2.13 2.13 2.12 2.11 2.10 2.09 2.08

0.0000 0.0009 0.0263 0.0031 0.0049 0.0243 0.0012 0.0123 0.0077 0.0000 0.0020 0.0008 0.0003 0.0053 0.0000 0.0014 0.0152 0.0000 0.0000 0.0038 0.0001 0.0092 0.0003 0.0002 0.0000 0.0054 0.0057 0.0003 0.0034 0.0017 0.0334 0.0010 0.0018 0.0009 0.0052 0.0001 0.0005 0.0012 0.0106 0.0095 0.0018 0.0048 0.0052 0.0000 0.0231

SNHG16 RP5-1014D13.2 ZNF561-AS1 INAFM2 RP11-400F19.8 RP4-594I10.3 HLA-DQB1-AS1 CTD-2377D24.6 ASMTL-AS1 RP5-1085F17.3 RP11-6N17.6 RP11-290D2.6 RP11-667K14.4 RP11-87H9.4 AC074117.10

10.46 1.63 1.17 3.10 1.04 1.64 1.06 1.44 2.18 1.18 5.81 64.88 17.80 2.96 1.63

21.72 3.38 2.44 6.42 2.14 3.36 2.17 2.92 4.42 2.40 11.77 131.02 35.82 5.94 3.26

2.08 2.08 2.08 2.07 2.06 2.05 2.04 2.03 2.03 2.03 2.02 2.02 2.01 2.01 2.01

0.0000 0.0000 0.0133 0.0096 0.0353 0.0044 0.0154 0.0319 0.0173 0.0058 0.0028 0.0039 0.0001 0.0139 0.0091

b) List of lncRNAs significantly overexpressed (1.5-2 fold) in NKTCL cases compared to those in normal NK cells

Gene_short_name RP11-108P20.3 AP003774.1 RP11-405M12.4 LINC00152 RP11-442H21.2 AC107081.5 RP11-603J24.17 RP11-977G19.5 CKMT2-AS1 RP11-46A10.5 LINC00998 RP11-589M4.1 AC005538.3 RP4-669L17.10 NEAT1 RP11-72I8.1 RP11-285F7.2 RP11-867G23.4 RP11-295P9.3 CTD-3185P2.1 CH17-340M24.3

Normal NK cell NKTCL median median expression level expression level (FPKM) (FPKM) 1.44 2.87 1.63 3.24 2.06 4.08 41.40 80.86 53.35 103.84 7.86 15.12 10.28 19.78 1.43 2.74 1.29 2.46 1.11 2.12 18.57 35.41 1.59 3.02 1.63 3.09 3.11 5.88 89.05 167.43 2.52 4.74 1.27 2.37 33.01 61.76 5.15 9.56 1.31 2.42 2.50 4.58

The ratio of median expression value (NKTCL/normal NK)

t-test

1.99 1.99 1.98 1.95 1.95 1.92 1.92 1.92 1.91 1.91 1.91 1.91 1.89 1.89 1.88 1.88 1.87 1.87 1.86 1.84 1.83

0.0286 0.0096 0.0390 0.0283 0.0003 0.0102 0.0015 0.0066 0.0044 0.0000 0.0342 0.0085 0.0080 0.0421 0.0082 0.0254 0.0103 0.0028 0.0294 0.0017 0.0003

MIR155HG RP13-131K19.2 RP11-135L13.4 CTD-2647L4.5 RP13-820C6.2 CTB-43P18.1 AC009120.6 SNHG21 RP11-798M19.3 RP11-228B15.4 RP1-151F17.2 RP11-12G12.7 CTD-2256P15.4 CTC-524C5.2 AP003068.9 RN7SL1 CTD-2545M3.2 CTD-2292P10.2 RP11-480A16.1 RP11-361L15.3 KB-1107E3.1 KDM4A-AS1 RP11-111M22.3 RP4-758J18.13 RP11-73M18.8 RP11-799B12.1 RP11-727A23.11 ENTPD3-AS1 CTB-31O20.3 AZIN1-AS1 CTC-425F1.4 RP11-256P1.1 AC068580.6 RP11-342K6.1 AF127577.10 GS1-124K5.4 RP11-400F19.6 GTF3C2-AS1 AC007383.4 OR2A1-AS1 LINC00339 SRP14-AS1 RP11-589M4.1 RP11-727F15.12 RP11-468E2.10

17.60 2.77 1.42 3.22 3.62 39.97 22.10 2.36 3.73 3.35 2.12 1.55 8.06 3.22 11.51 31.66 8.90 1.01 1.35 6.12 1.03 4.54 2.73 1.68 7.38 7.71 1.20 1.54 3.93 1.19 34.73 4.65 1.48 1.77 5.48 1.55 1.87 2.41 1.37 1.31 9.26 1.56 4.79 1.81 1.05

32.08 5.03 2.58 5.82 6.50 71.69 39.62 4.23 6.67 5.99 3.75 2.73 14.17 5.62 19.95 54.83 15.39 1.75 2.31 10.51 1.77 7.70 4.63 2.84 12.30 12.72 1.97 2.53 6.45 1.95 56.75 7.50 2.40 2.85 8.79 2.47 2.95 3.75 2.13 2.05 14.40 2.41 7.36 2.77 1.61

1.82 1.82 1.82 1.81 1.79 1.79 1.79 1.79 1.79 1.79 1.77 1.76 1.76 1.75 1.73 1.73 1.73 1.73 1.72 1.72 1.72 1.70 1.70 1.69 1.67 1.65 1.65 1.64 1.64 1.64 1.63 1.61 1.61 1.61 1.60 1.59 1.58 1.56 1.56 1.56 1.55 1.55 1.54 1.53 1.53

0.0339 0.0189 0.0110 0.0299 0.0401 0.0005 0.0037 0.0130 0.0008 0.0348 0.0205 0.0280 0.0212 0.0066 0.0014 0.0165 0.0012 0.0239 0.0295 0.0035 0.0059 0.0010 0.0472 0.0283 0.0207 0.0457 0.0479 0.0056 0.0205 0.0101 0.0225 0.0191 0.0242 0.0126 0.0343 0.0288 0.0075 0.0064 0.0137 0.0323 0.0416 0.0002 0.0049 0.0155 0.0212

RP11-63M22.2 SNHG6

10.23 74.35

15.58 112.54

1.52 1.51

0.0003 0.0032

Supplemental Table 3 a) lncRNAs significantly downregulated (> 2-fold) in NKTCL cases compared to those in normal NK cells lncRNA name RP11-932O9.9 RP11-612B6.2 AC006129.2 RP11-229E13.4 CTD-3252C9.4 PRKCQ-AS1 LINC00893 RP11-686D22.9 RP11-67A1.2 RP11-539L10.2 CTC-246B18.8 RP11-540B6.6 AC008993.2 RP11-463J10.3 RP11-73E17.2 AC093484.4 AC068831.15 RP5-1180D12.1 LINC01588 ZMYM4-AS1 MDC1-AS1 RP11-227G15.3 RP11-875O11.1 RP11-756P10.6 LINC00667 CTD-3126B10.1 PKD1P6 RP11-793H13.3 RP11-700J17.2 CTB-5E10.3 RP11-849H4.4 CTB-60E11.9 RP11-902B17.1 RP11-362K14.5 ZBTB11-AS1 CTD-2013N24.2 RP11-69E11.4 AC006547.13

Normal NK cell median expression level (FPKM) 73.98 204.47 55.60 483.52 15.24 59.86 9.15 6.64 11.83 10.58 4.94 6.97 7.34 104.72 7.33 3.19 32.38 20.72 7.66 3.42 4.12 133.19 5.01 3.28 19.16 10.48 6.67 3.17 2.79 15.40 5.35 2.66 3.36 3.72 3.01 22.39 5.20 5.42

NKTCL median expression level (FPKM) 1.04 7.26 8.08 71.61 2.60 10.28 1.60 1.39 2.55 2.52 1.23 1.74 1.92 27.44 2.06 1.05 10.84 6.97 2.61 1.23 1.57 52.16 1.96 1.33 8.07 4.56 2.95 1.40 1.25 7.14 2.49 1.24 1.58 1.75 1.44 10.89 2.54 2.66

The ratio of median expression value (NKTCL/normal NK) 0.01 0.04 0.15 0.15 0.17 0.17 0.17 0.21 0.22 0.24 0.25 0.25 0.26 0.26 0.28 0.33 0.33 0.34 0.34 0.36 0.38 0.39 0.39 0.40 0.42 0.43 0.44 0.44 0.45 0.46 0.46 0.47 0.47 0.47 0.48 0.49 0.49 0.49

t-test 0.041154 0.023023 0.039223 0.033174 8.11E-08 0.044967 0.038119 0.014688 0.001909 4.09E-05 0.038403 0.033216 0.024556 1.25E-09 0.024918 0.000425 0.014444 5.4E-06 0.001103 0.000529 0.000591 0.013205 0.041179 0.002872 0.048139 0.004672 0.010637 0.020596 0.02361 0.010282 0.006227 2.78E-05 0.004127 0.030268 0.039914 1.74E-08 0.027211 0.028088

b) lncRNAs significantly downregulated (1.5 to 2-fold) in NKTCL cases compared to those in normal NK cells

lncRNA name C5orf66 RP11-20I23.6 CTB-5E10.3 NDUFA6-AS1 CTD-2020K17.3 RP11-566E18.1 VIM-AS1 LA16c-407A10.3 LINC00863 SVIL-AS1 RP4-681N20.5 RP11-463O12.3 ACAP2-IT1 AC005606.14 AC002398.11 RP11-817O13.8 RP11-278C7.5 RP11-159G9.5 EDRF1-AS1 CRHR1-IT1 RP11-35G9.3 RP11-707G14.1 RP11-76I23.7 RP1-50O24.6 RP11-296O14.3 FGD5-AS1 TUG1 RP11-629N8.5

Normal NK cell median expression level (FPKM) 8.18 3.32 9.57 3.41 4.45 1.96 7.32 5.55 2.33 5.85 1.93 20.48 1.86 8.73 1.79 2.44 5.22 7.06 3.36 8.96 5.64 10.83 3.83 1.98 1.93 49.16 55.96 29.31

NKTCL median expression level (FPKM) 4.07 1.70 4.92 1.76 2.32 1.03 3.87 2.95 1.26 3.16 1.06 11.27 1.03 4.85 1.00 1.42 3.03 4.14 1.99 5.38 3.48 6.71 2.41 1.25 1.23 31.54 36.07 19.45

The ratio of median expression value (NKTCL/normal NK) 0.50 0.51 0.51 0.52 0.52 0.52 0.53 0.53 0.54 0.54 0.55 0.55 0.55 0.56 0.56 0.58 0.58 0.59 0.59 0.60 0.62 0.62 0.63 0.63 0.64 0.64 0.64 0.66

t-test 5.97E-05 0.003425 0.000373 0.004337 0.02278 0.00385 0.049349 0.032878 1.78E-06 0.011828 0.005912 0.014921 0.002417 0.019822 1.64E-05 0.025111 0.015909 0.003405 0.028812 0.039732 0.005916 0.048422 0.041627 0.048474 0.001614 0.015844 0.048427 0.022051